scholarly journals Temporal profiling of redox-dependent heterogeneity in single cells

2017 ◽  
Author(s):  
Meytal Radzinski ◽  
Rosi Fasler ◽  
Ohad Yogev ◽  
William Breuer ◽  
Nadav Shai ◽  
...  
Keyword(s):  
Single Cells ◽  
Redox Homeostasis ◽  
Redox Status ◽  
Yeast Cells ◽  
Protein Homeostasis ◽  
Cellular Functions ◽  
Defense Proteins ◽  
Cellular Redox ◽  
Oxidation Status ◽  
Logarithmic Growth

AbstractCellular redox status affects diverse cellular functions, including proliferation, protein homeostasis, and aging. Thus, individual differences in redox status can give rise to distinct sub-populations even among cells with identical genetic backgrounds. Here, we have created a novel methodology to track redox status at single cell resolution using the redox-sensitive probe roGFP. Our method allows identification and sorting of sub-populations with different oxidation levels in either the cytosol, mitochondria or peroxisomes. Using this approach we defined redox-dependent heterogeneity of yeast cells, and characterized growth, as well as proteomic and transcriptomic profiles of subpopulations of cells that differ in their redox status, but are similar in age. We report that, starting in late logarithmic growth, cells of the same age have a bi-modal distribution of oxidation status. A comparative proteomic analysis between these populations identified three key proteins, Hsp30, Dhh1, and Pnc1, which affect basal oxidation levels and may serve as first line of defense proteins in redox homeostasis.

scholarly journals Temporal profiling of redox-dependent heterogeneity in single cells

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Meytal Radzinski ◽  
Rosi Fassler ◽  
Ohad Yogev ◽  
William Breuer ◽  
Nadav Shai ◽  
...  
Keyword(s):  
Single Cells ◽  
Redox Homeostasis ◽  
Redox Status ◽  
Yeast Cells ◽  
Protein Homeostasis ◽  
Cellular Functions ◽  
Defense Proteins ◽  
Cellular Redox ◽  
Oxidation Status ◽  
Logarithmic Growth

Cellular redox status affects diverse cellular functions, including proliferation, protein homeostasis, and aging. Thus, individual differences in redox status can give rise to distinct sub-populations even among cells with identical genetic backgrounds. Here, we have created a novel methodology to track redox status at single cell resolution using the redox-sensitive probe Grx1-roGFP2. Our method allows identification and sorting of sub-populations with different oxidation levels in either the cytosol, mitochondria or peroxisomes. Using this approach, we defined a redox-dependent heterogeneity of yeast cells and characterized growth, as well as proteomic and transcriptomic profiles of distinctive redox subpopulations. We report that, starting in late logarithmic growth, cells of the same age have a bi-modal distribution of oxidation status. A comparative proteomic analysis between these populations identified three key proteins, Hsp30, Dhh1, and Pnc1, which affect basal oxidation levels and may serve as first line of defense proteins in redox homeostasis.

scholarly journals Post-Translational S-Nitrosylation of Proteins in Regulating Cardiac Oxidative Stress

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1051 ◽  
Author(s):  
Xiaomeng Shi ◽  
Hongyu Qiu
Keyword(s):  
Therapeutic Potential ◽  
Heart Diseases ◽  
Redox Homeostasis ◽  
Redox Status ◽  
Cardiac Protection ◽  
Cellular Functions ◽  
Post Translational Modifications ◽  
Cellular Redox ◽  
Novel Therapeutic Strategies

Like other post-translational modifications (PTMs) of proteins, S-nitrosylation has been considered a key regulatory mechanism of multiple cellular functions in many physiological and disease conditions. Emerging evidence has demonstrated that S-nitrosylation plays a crucial role in regulating redox homeostasis in the stressed heart, leading to discoveries in the mechanisms underlying the pathogenesis of heart diseases and cardiac protection. In this review, we summarize recent studies in understanding the molecular and biological basis of S-nitrosylation, including the formation, spatiotemporal specificity, homeostatic regulation, and association with cellular redox status. We also outline the currently available methods that have been applied to detect S-nitrosylation. Additionally, we synopsize the up-to-date studies of S-nitrosylation in various cardiac diseases in humans and animal models, and we discuss its therapeutic potential in cardiac protection. These pieces of information would bring new insights into understanding the role of S-nitrosylation in cardiac pathogenesis and provide novel avenues for developing novel therapeutic strategies for heart diseases.

scholarly journals Linkage between Carbon Metabolism, Redox Status and Cellular Physiology in the Yeast Saccharomyces cerevisiae Devoid of SOD1 or SOD2 Gene

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 780 ◽  
Author(s):  
Roman Maslanka ◽  
Renata Zadrag-Tecza ◽  
Magdalena Kwolek-Mirek
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Carbon Metabolism ◽  
Redox Homeostasis ◽  
Carbon Sources ◽  
Pyridine Nucleotide ◽  
Redox Status ◽  
Yeast Cells ◽  
Yeast Saccharomyces Cerevisiae ◽  
Cellular Physiology ◽  
Respiratory Conditions

Saccharomyces cerevisiae yeast cells may generate energy both by fermentation and aerobic respiration, which are dependent on the type and availability of carbon sources. Cells adapt to changes in nutrient availability, which entails the specific costs and benefits of different types of metabolism but also may cause alteration in redox homeostasis, both by changes in reactive oxygen species (ROS) and in cellular reductant molecules contents. In this study, yeast cells devoid of the SOD1 or SOD2 gene and fermentative or respiratory conditions were used to unravel the connection between the type of metabolism and redox status of cells and also how this affects selected parameters of cellular physiology. The performed analysis provides an argument that the source of ROS depends on the type of metabolism and non-mitochondrial sources are an important pool of ROS in yeast cells, especially under fermentative metabolism. There is a strict interconnection between carbon metabolism and redox status, which in turn has an influence on the physiological efficiency of the cells. Furthermore, pyridine nucleotide cofactors play an important role in these relationships.

scholarly journals Differential regulation of Ca2+ influx by ORAI channels mediates enamel mineralization

2019 ◽  
Vol 12 (578) ◽  
pp. eaav4663 ◽  
Author(s):  
Miriam Eckstein ◽  
Martin Vaeth ◽  
Francisco J. Aulestia ◽  
Veronica Costiniti ◽  
Serena N. Kassam ◽  
...  
Keyword(s):  
Consumption Rate ◽  
Redox Homeostasis ◽  
Direct Interaction ◽  
Redox Status ◽  
Cellular Functions ◽  
Enamel Defects ◽  
Targeted Deletion ◽  
Anhidrotic Ectodermal Dysplasia ◽  
Enamel Mineralization

Store-operated Ca2+ entry (SOCE) channels are highly selective Ca2+ channels activated by the endoplasmic reticulum (ER) sensors STIM1 and STIM2. Their direct interaction with the pore-forming plasma membrane ORAI proteins (ORAI1, ORAI2, and ORAI3) leads to sustained Ca2+ fluxes that are critical for many cellular functions. Mutations in the human ORAI1 gene result in immunodeficiency, anhidrotic ectodermal dysplasia, and enamel defects. In our investigation of the role of ORAI proteins in enamel, we identified enamel defects in a patient with an ORAI1 null mutation. Targeted deletion of the Orai1 gene in mice showed enamel defects and reduced SOCE in isolated enamel cells. However, Orai2−/− mice showed normal enamel despite having increased SOCE in the enamel cells. Knockdown experiments in the enamel cell line LS8 suggested that ORAI2 and ORAI3 modulated ORAI1 function, with ORAI1 and ORAI2 being the main contributors to SOCE. ORAI1-deficient LS8 cells showed altered mitochondrial respiration with increased oxygen consumption rate and ATP, which was associated with altered redox status and enhanced ER Ca2+ uptake, likely due to S-glutathionylation of SERCA pumps. Our findings demonstrate an important role of ORAI1 in Ca2+ influx in enamel cells and establish a link between SOCE, mitochondrial function, and redox homeostasis.

scholarly journals Redox Potential of Antioxidants in Cancer Progression and Prevention

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1156
Author(s):  
Sajan George ◽  
Heidi Abrahamse
Keyword(s):  
Oxidative Stress ◽  
Cancer Progression ◽  
Natural Antioxidants ◽  
Redox Balance ◽  
Redox Status ◽  
Enzyme Activation ◽  
Metabolic Reprogramming ◽  
Cellular Functions ◽  
Cellular Redox ◽  
The Right

The benevolent and detrimental effects of antioxidants are much debated in clinical trials and cancer research. Several antioxidant enzymes and molecules are overexpressed in oxidative stress conditions that can damage cellular proteins, lipids, and DNA. Natural antioxidants remove excess free radical intermediates by reducing hydrogen donors or quenching singlet oxygen and delaying oxidative reactions in actively growing cancer cells. These reducing agents have the potential to hinder cancer progression only when administered at the right proportions along with chemo-/radiotherapies. Antioxidants and enzymes affect signal transduction and energy metabolism pathways for the maintenance of cellular redox status. A decline in antioxidant capacity arising from genetic mutations may increase the mitochondrial flux of free radicals resulting in misfiring of cellular signalling pathways. Often, a metabolic reprogramming arising from these mutations in metabolic enzymes leads to the overproduction of so called ’oncometabolites’ in a state of ‘pseudohypoxia’. This can inactivate several of the intracellular molecules involved in epigenetic and redox regulations, thereby increasing oxidative stress giving rise to growth advantages for cancerous cells. Undeniably, these are cell-type and Reactive Oxygen Species (ROS) specific, which is manifested as changes in the enzyme activation, differences in gene expression, cellular functions as well as cell death mechanisms. Photodynamic therapy (PDT) using light-activated photosensitizing molecules that can regulate cellular redox balance in accordance with the changes in endogenous ROS production is a solution for many of these challenges in cancer therapy.

scholarly journals Expression of the trxC Gene of Rhodobacter capsulatus: Response to Cellular Redox Status Is Mediated by the Transcriptional Regulator OxyR

2006 ◽  
Vol 188 (21) ◽  
pp. 7689-7695 ◽  
Author(s):  
Tanja Zeller ◽  
Kuanyu Li ◽  
Gabriele Klug
Keyword(s):  
Redox Regulation ◽  
Molecular Mechanisms ◽  
Rhodobacter Capsulatus ◽  
Transcriptional Regulator ◽  
Redox Status ◽  
Cellular Functions ◽  
Cellular Redox

ABSTRACT Despite the importance of thioredoxins in cellular functions, little is known about the regulation of trx genes. To understand the molecular mechanisms involved in the regulation of the Rhodobacter capsulatus trxC gene, the expression of this gene was investigated. We describe OxyR-dependent redox regulation of the trxC gene that adjusts the levels of thioredoxins in the cell.

scholarly journals Oxidative Stress-Mediated Skeletal Muscle Degeneration: Molecules, Mechanisms, and Therapies

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Min Hee Choi ◽  
Jin Rong Ow ◽  
Nai-Di Yang ◽  
Reshma Taneja
Keyword(s):  
Oxidative Stress ◽  
Molecular Level ◽  
Redox Homeostasis ◽  
Redox Status ◽  
Muscle Degeneration ◽  
Dystrophic Muscle ◽  
Telomere Shortening ◽  
Cellular Redox ◽  
Pathological Conditions

Oxidative stress is a loss of balance between the production of reactive oxygen species during cellular metabolism and the mechanisms that clear these species to maintain cellular redox homeostasis. Increased oxidative stress has been associated with muscular dystrophy, and many studies have proposed mechanisms that bridge these two pathological conditions at the molecular level. In this review, the evidence indicating a causal role of oxidative stress in the pathogenesis of various muscular dystrophies is revisited. In particular, the mediation of cellular redox status in dystrophic muscle by NF-κB pathway, autophagy, telomere shortening, and epigenetic regulation are discussed. Lastly, the current stance of targeting these pathways using antioxidant therapies in preclinical and clinical trials is examined.

scholarly journals Time line of redox events in aging postmitotic cells

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Nicolas Brandes ◽  
Heather Tienson ◽  
Antje Lindemann ◽  
Victor Vitvitsky ◽  
Dana Reichmann ◽  
...  
Keyword(s):  
Redox Homeostasis ◽  
Yeast Cells ◽  
Free Radical Theory ◽  
Radical Theory ◽  
Cellular Redox ◽  
Time Line ◽  
Present Evidence ◽  
Cellular Processes ◽  
Theory Of Aging ◽  
Substantial Drop

The precise roles that oxidants play in lifespan and aging are still unknown. Here, we report the discovery that chronologically aging yeast cells undergo a sudden redox collapse, which affects over 80% of identified thiol-containing proteins. We present evidence that this redox collapse is not triggered by an increase in endogenous oxidants as would have been postulated by the free radical theory of aging. Instead it appears to be instigated by a substantial drop in cellular NADPH, which normally provides the electron source for maintaining cellular redox homeostasis. This decrease in NADPH levels occurs very early during lifespan and sets into motion a cascade that is predicted to down-regulate most cellular processes. Caloric restriction, a near-universal lifespan extending measure, increases NADPH levels and delays each facet of the cascade. Our studies reveal a time line of events leading up to the system-wide oxidation of the proteome days before cell death.

scholarly journals Redox Systems in Botrytis cinerea: Impact on Development and Virulence

2014 ◽  
Vol 27 (8) ◽  
pp. 858-874 ◽  
Author(s):  
Anne Viefhues ◽  
Jens Heller ◽  
Nora Temme ◽  
Paul Tudzynski
Keyword(s):  
Botrytis Cinerea ◽  
Redox Homeostasis ◽  
Thioredoxin Reductase ◽  
Redox System ◽  
Redox Status ◽  
Redox Systems ◽  
Gene Encoding ◽  
Cellular Redox ◽  
Thioredoxin System ◽  
The Impact

The thioredoxin system is of great importance for maintenance of cellular redox homeostasis. Here, we show that it has a severe influence on virulence of Botrytis cinerea, demonstrating that redox processes are important for host-pathogen interactions in this necrotrophic plant pathogen. The thioredoxin system is composed of two enzymes, the thioredoxin and the thioredoxin reductase. We identified two genes encoding for thioredoxins (bctrx1, bctrx2) and one gene encoding for a thioredoxin reductase (bctrr1) in the genome of B. cinerea. Knockout mutants of bctrx1 and bctrr1 were severely impaired in virulence and more sensitive to oxidative stress. Additionally, Δbctrr1 showed enhanced H2O2 production and retarded growth. To investigate the impact of the second major cellular redox system, glutathione, we generated deletion mutants for two glutathione reductase genes. The effects were only marginal; deletion of bcglr1 resulted in reduced germination and, correspondingly, to retarded infection as well as reduced growth on minimal medium, whereas bcglr2 deletion had no distinctive phenotype. In summary, we showed that the balanced redox status maintained by the thioredoxin system is essential for development and pathogenesis of B. cinerea, whereas the second major cellular redox system, the glutathione system, seems to have only minor impact on these processes.

Antioxidant metal oxide nanozymes: role in cellular redox homeostasis and therapeutics

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Namrata Singh
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Metal Oxide ◽  
Redox Homeostasis ◽  
Redox Status ◽  
Artificial Enzymes ◽  
Oxygen Species ◽  
First Line ◽  
Cellular Redox ◽  
Tremendous Progress

AbstractNanomaterials with enzyme-like activity, generally referred to as ‘nanozymes’, find myriad potential in various biomedical fields. More importantly, the nanoparticles that can functionally mimic the activity of cellular antioxidant enzymes attract tremendous interest owing to their possible therapeutic candidature in oxidative stress-mediated disorders. Oxidative stress culminating due to excess reactive oxygen species (ROS) level and dysregulated cellular antioxidant machinery is implicated in the development and progression of various pathophysiological disorders such as cancer, diabetes, cardiovascular and neurodegenerative diseases. Moreover, the optimum essentiality of ROS due to its pivotal role in cell signaling evokes the requirement of novel artificial antioxidant enzymes that can circumvent the detrimental effects of enhanced ROS levels without perturbing the basal redox status of cells. In recent years, the fast emanating artificial enzymes, i.e. nanozymes with antioxidant enzyme-like activity, has made tremendous progress with their broad applications in therapeutics, diagnostic medicine, bio-sensing, and immunoassay. Among various antioxidant nanoparticles reported till-date, the metal oxide nanozymes have emerged as the most efficient and successful candidates in mimicking the activity of first-line defense antioxidant enzymes, i.e. superoxide dismutase, catalase, and glutathione peroxidase. This review intends to exclusively highlight the development of representative metal oxide-based antioxidant nanozymes capable of maintaining the cellular redox homeostasis and their potential therapeutic significance.

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